V3-independent determinants of macrophage tropism in a primary human immunodeficiency virus type 1 isolate.

Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.

V3-independent determinants of macrophage tropism in a primary human immunodeficiency virus type 1 isolate.

J Virol. 1995 Mar;69(3):1755-61. Unique Identifier : AIDSLINE MED/95156606
Kim FM; Kolson DL; Balliet JW; Srinivasan A; Collman RG; Department of Medicine, University of Pennsylvania School of; Medicine, Philadelphia 19104-6076.

Abstract: Human immunodeficiency virus type 1 isolates differ in their ability to productively infect macrophages, and several groups have mapped the genetic basis for macrophage tropism to regions of env that include the third hypervariable region (V3 loop). We recently described a primary isolate (89.6) which is highly macrophage tropic and yet differs from other macrophage-tropic strains studied in that it is cytopathic in T cells. Genetic mapping of macrophage tropism determinants in this virus was done by using chimeras generated with the prototypic non-macrophage-tropic strain HXB2. Replacement of a 2.7-kb env-containing region of HXB with corresponding sequences from 89.6 conferred the macrophage-tropic phenotype, but insertion of the 89.6 V3 loop along with V4/V5 sequences did not. Conversely, placement of HXB sequences that included V3 into 89.6 did not impair this strain's ability to replicate in macrophages. Sequence analysis of V3 shows that 89.6 differs markedly from previously described macrophage-tropic consensus sequences and that it is more similar to highly charged non-macrophage-tropic strains. This suggests either that macrophage tropism is defined by structural determinants resulting from complex interactions among multiple env regions rather than V3 sequence-specific requirements or that there are multiple mechanisms by which different strains may establish productive macrophage infection. In addition, because the HXB V3 loop supports productive macrophage infection in the background of 89.6, phenotypic characterization of V3 sequences should be considered specific to the viral context in which they are placed.

Keywords: Amino Acid Sequence Base Sequence Chimeric Proteins Comparative Study Consensus Sequence DNA Primers/CHEMISTRY Human HIV Envelope Protein gp120/*PHYSIOLOGY HIV-1/*GROWTH & DEVELOPMENT In Vitro Macrophages/*MICROBIOLOGY Molecular Sequence Data Sequence Alignment Sequence Homology, Amino Acid Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Virus Replication JOURNAL ARTICLE
950530
M9550414

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